Therapeutic Hypothermia to Improve Survival After Cardiac Arrest in Pediatric Patients-THAPCA-IH [In Hospital] Trial: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Therapeutic Hypothermia to Improve Survival After Cardiac Arrest in Pediatric Patients-THAPCA-IH [In Hospital] Trial (NCT00880087), a randomized na study. The primary outcome is Survival With Good Neurobehavioral Outcome.

2. Clinical Question

The clinical rationale described in the record is that therapeutic hypothermia has been used in adults after cardiac arrest, while this trial evaluates its use in infants and children after an in-hospital arrest. The stated aims include evaluating survival and risk of brain injury. Those aims are not themselves results: the available record does not establish whether the groups differed on the primary endpoint or on the broader aims. It also does not identify a numerical estimate of the treatment contrast or its precision.

3. Trial Design

This was a randomized, single-masked, parallel-group trial comparing therapeutic hypothermia with therapeutic normothermia after in-hospital cardiac arrest. The registry lists enrollment of 329 and identifies the study as completed. The listed start is 2009-09, and the primary completion date is 2016-02. The sponsor was the University of Michigan. The phase is listed as NA.

Random allocation means that assignment to the two interventions was intended to occur by chance. In general, randomization can help balance measured and unmeasured characteristics across groups at the time of assignment, but it does not guarantee identical groups. The record does not report the randomization procedure, allocation concealment, or whether the analysis followed the randomized assignment regardless of treatment received. The masking field says single; which people were masked is not reported in the registry record.

The parallel-group structure means participants were assigned to one intervention group rather than crossing between both interventions as part of the design. The listed interventions are procedures. The record’s arm descriptions state that participants received the respective temperature-management approach after cardiac arrest, but it does not report details such as treatment duration, target temperatures, or adherence.

The primary endpoint is a participant count for survival with a good neurobehavioral outcome, assessed at the one-year anniversary of cardiac arrest with a valid VABS-II assessment in a specified window. The registry also lists secondary outcomes concerning survival, change in neurobehavioral function from before cardiac arrest to 12 months after arrest, and neuropsychological scores among survivors. It lists 5 outcome measures and 4 analyses, but does not describe how those measures map to analyses. The numerical primary outcome findings, treatment-effect estimate, uncertainty interval, and analysis procedure are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Subjects with baseline VABS-II \>= 70, OR unavailable baseline VABS-II but Pediatric Overall Performance Category (POPC) score and Pediatric Cerebral Overall Performance Category (PCPC) both reflecting none or mild disability (1 or 2), are eligible for the primary analysis. Population is analysis-eligible patients with available primary outcome.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Survival With Good Neurobehavioral Outcome, measured over Survival was assessed at one-year anniversary of cardiac arrest; among survivors at this one-year anniversary, the VABS-II valid assessment window ranged from 30 days prior to until 183 days after the one-year anniversary date..

The primary endpoint is “Survival With Good Neurobehavioral Outcome,” expressed as a count of participants. A participant had to be alive at the one-year anniversary of cardiac arrest and have a standardized VABS-II score of 70 or greater. The valid assessment window ran from 30 days before to 183 days after that anniversary. The record states that higher VABS-II values represent a better outcome.

This combined endpoint addresses survival and function together. Counting survival alone would not describe neurobehavioral status among survivors; assessing function only among survivors would not represent participants who died. The combined definition sets a specific threshold for what counts as a good outcome and applies it alongside survival. In general, such a threshold-based endpoint can be easier to interpret as a participant count, while also discarding detail about differences in scores on either side of the threshold. This is a general statistical consideration, not a finding about the trial’s results.

Eligibility for the primary analysis was further defined using baseline function: a baseline VABS-II score of at least 70, or an unavailable baseline VABS-II score with POPC and PCPC scores both indicating none or mild disability, coded as 1 or 2. The registry’s description of the analysis population is cut off after “analysis-el,” so the full wording is not reported in the registry record. No group counts, effect estimate, confidence interval, or test result for the primary endpoint are reported.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a randomized parallel-group comparison with a single-masking designation. These are design features, not a complete statistical analysis plan. The allocation method beyond the word “randomized,” the identity of the masked parties, and the planned primary analysis procedure are not reported in the registry record.

What does a participant-count endpoint mean?

The primary measure is the count of participants who meet the defined outcome: survival at the one-year anniversary together with a VABS-II score of 70 or greater in the valid assessment window. In general, a binary outcome places each participant into one of two categories for analysis, such as meeting or not meeting the endpoint. A count alone is not enough to compare groups statistically: interpretation also requires the relevant group denominators and a defined comparison method. The primary group counts, denominators, and comparison result are not reported in the registry record.

The endpoint is a composite in the sense that it requires both survival and a qualifying neurobehavioral assessment. That structure can represent more than one aspect of outcome in a single criterion. In general, however, a combined endpoint needs careful interpretation because a group contrast could reflect different contributions from its component conditions. The registry record does not report component-specific primary outcome results.

Why does the assessment window matter?

The endpoint ties survival to the one-year anniversary of arrest and allows a VABS-II assessment from 30 days before to 183 days after that anniversary. A defined window makes the timing rule part of the endpoint rather than treating every assessment date as interchangeable. In general, measurements taken at different times can reflect different stages of recovery or follow-up. The record does not report how many assessments fell at particular times, how assessments outside the window were handled, or how missing VABS-II assessments were treated.

What can be inferred from randomization?

In general, random assignment supports a comparison of groups as assigned, because assignment is not deliberately based on participants’ prognosis. That rationale depends on the actual conduct and analysis of the trial. The registry does not report the sequence-generation or concealment procedures, whether participants were analyzed according to assignment, or the handling of deviations from assigned intervention. It is therefore possible to describe the design as randomized, but not to fill in those details.

Likewise, “single” masking indicates a masking designation but does not say who was unaware of group assignment. In general, masking can reduce some forms of biased treatment, assessment, or reporting, depending on who is masked and how the outcome is measured. The record does not identify the masked group or describe any measures used to maintain masking.

What does a confidence interval contribute?

In general, an estimated treatment contrast describes the observed difference between groups according to a chosen measure, while a confidence interval conveys statistical uncertainty around that estimate. The width of an interval is informative about precision; it does not by itself establish clinical importance. A p-value addresses the compatibility of the data with a null hypothesis under the analysis assumptions, but it does not give the probability that the null hypothesis is true. No primary estimate, confidence interval, or p-value is reported in the registry record, so these features cannot be interpreted for the primary endpoint.

How should the planning illustration be understood?

The registry’s sample-size assumptions describe a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. The illustration is described as targeting a stated fraction of the observed effect. Such a calculation is a planning exercise rather than an observed trial result. Its sample sizes are not observed power, and they do not replace the trial’s primary estimate or its uncertainty. The record does not report the trial’s own sample-size justification or design assumptions. The primary outcome has several categories or time points and was not reduced to one comparison for the posted calculation, so there is no single primary-outcome planning comparison to interpret from that illustration.

For a binary outcome, a sample-size calculation ordinarily depends on assumptions about event frequencies, the target effect, significance level, allocation, and desired power. This is general statistical context; the registry identifies only the listed assumptions for its planning illustration, not the full protocol rationale. No calculated sample-size result is stated in the registry record.

Why might over-dispersion matter?

Over-dispersion is a general issue for count data when observed variability exceeds what a chosen model expects. It can make standard errors too small if a model assumes less variability than the data contain. The primary outcome is a participant count for a binary criterion, not a reported recurrent-event rate or other over-dispersed count process. The record does not report a model or an over-dispersion assessment; no claim about either can be made for this trial.

Overall, the design details support a concise account of the randomized comparison, but the registry record does not give the analysis details needed to reproduce or evaluate a primary statistical test. The missing results also preclude describing statistical significance, effect size, or precision.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 5 outcome measures and 4 analyses. The secondary outcomes include survival, change in neurobehavioral function from before cardiac arrest to 12 months after arrest, and neuropsychological scores among participants who survive. The record does not describe how the outcome measures correspond to the analyses, which outcomes were included in each analysis, or which comparisons were designated as confirmatory.

Multiplicity arises in general when several outcomes, time points, or comparisons are tested. If many tests are conducted, the chance of at least one apparently notable result can increase unless the analysis plan accounts for the testing structure. This general issue does not show that any particular result is false; it explains why a prespecified plan and transparent reporting are useful. A multiplicity adjustment or strategy is not reported in the registry record.

The primary outcome definition includes survival at a specified anniversary and a neurobehavioral score assessed within a defined window. The registry also describes several secondary outcomes, but does not state how repeated measurements, multiple time points, or survivor-only assessments were handled statistically. The primary analysis population is partly described by baseline VABS-II, POPC, and PCPC criteria, but the record’s population wording ends incompletely. The number eligible for that analysis and the exact analysis population are not reported in the registry record.

Missing-data methods are also not reported in the registry record. In general, missing outcome assessments can affect both the number analyzed and the interpretation of a group comparison, especially when assessment availability is related to participant status or outcome. The endpoint’s assessment window is stated, but rules for unavailable or out-of-window assessments, imputation, censoring, or sensitivity analyses are not given. The record therefore does not permit an assessment of how missing outcome data were addressed or how robust the primary comparison would be to alternative assumptions.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cardiac arrest (11.2%), anoxic brain damage (5.0%), hypoxic encephalopathy (3.8%), pulmonary hemorrhage (3.1%), bradycardia (2.5%).

The registry lists serious adverse events and other adverse events separately for the two groups. Serious adverse events affected 85 of 161 participants assigned to therapeutic hypothermia and 91 of 160 assigned to therapeutic normothermia. Other adverse events affected 151 of 161 and 146 of 160 participants, respectively. The record also lists 82 deaths in the therapeutic hypothermia group and 84 in the therapeutic normothermia group.

Among the listed serious-event terms, cardiac arrest is reported as 11.2%, anoxic brain damage as 5.0%, hypoxic encephalopathy as 3.8%, pulmonary hemorrhage as 3.1%, bradycardia as 2.5%, and renal failure as 2.5%. The registry record does not explain the denominator or whether these percentages refer to participants, events, or another calculation. It also does not report a statistical comparison or uncertainty interval for these terms.

These figures are descriptive counts and percentages. They should not be read as adjusted treatment effects or as evidence that the interventions caused or prevented an event. The record does not report event timing, severity distributions beyond the serious-event classification, or methods for comparing safety outcomes. Death counts are listed separately and should not be substituted for the primary endpoint, which also requires a qualifying neurobehavioral assessment.

12. What the Result Does, and Does Not, Mean

The posted record establishes that a randomized, single-masked, parallel-group trial compared therapeutic hypothermia with therapeutic normothermia after in-hospital cardiac arrest in pediatric patients. It defines the primary endpoint as survival at the one-year anniversary together with a VABS-II score of 70 or greater within the specified assessment window. It also reports selected adverse-event counts and serious-event terms.

It does not report the primary endpoint counts by group, a treatment-effect estimate, a confidence interval, or a p-value. Therefore, the primary comparison’s direction, magnitude, statistical precision, and compatibility with a null effect cannot be described from the registry record. The absence of a posted result is not evidence that the groups were the same, and the stated trial objective is not evidence that one intervention had a particular effect.

The safety counts provide a descriptive account of participants affected by serious and other adverse events, along with listed deaths. They do not by themselves establish whether a difference between groups is statistically reliable or attributable to the assigned intervention. The listed serious-event percentages also lack a stated denominator in the record, which limits interpretation of those values.

In general, treatment effects should be interpreted with attention to the outcome definition, analysis population, uncertainty, missing data, and the analysis plan. Here, some of those elements are defined, while key results and methods are not reported. The primary eligibility criteria are stated, but the full analysis-population wording is truncated. The treatment details and masking roles are also not specified. These gaps limit what can be concluded about the trial’s findings, not the clinical importance of the question it set out to address.

The registry’s completed status and enrollment figure do not resolve these limitations. They describe trial administration, not the primary outcome result. A full interpretation would require the primary group results and the methods used to analyze them, neither of which is reported in the registry record.

13. Why This Trial Matters Statistically

This trial addresses a difficult statistical and clinical measurement problem: evaluating outcomes after pediatric cardiac arrest requires attention to survival as well as function. The primary endpoint combines survival at the one-year anniversary with a defined VABS-II threshold, and the registry states the window in which that assessment could be valid. Those details make the outcome rule explicit and show that the comparison was not simply a count of survivors.

The design also illustrates why analysis populations matter. Eligibility for the primary analysis depended on baseline function measures, with an alternative criterion when baseline VABS-II was unavailable. That approach defines a target subgroup, but the full population description is cut off and the number eligible is not reported. Without the analysis denominator and group results, readers cannot determine how the endpoint was evaluated in the eligible population.

From a statistical reporting perspective, the record contains a clear design label and endpoint definition but lacks the primary estimate and its uncertainty. Those are central to distinguishing the size of an observed contrast from its precision. The listed adverse-event counts contribute safety context, yet they do not fill the gap in the primary efficacy comparison or provide inferential comparisons on their own.

The registry also lists multiple outcome measures and analyses without describing their mapping or a multiplicity strategy. That makes it difficult to understand how the full set of outcomes was organized statistically. The record’s planning illustration is explicitly separate from the trial’s own design rationale and is not a substitute for observed outcome estimates.

As a statistical case, the record highlights the value of reporting endpoint definitions, analysis populations, denominators, treatment contrasts, uncertainty intervals, and missing-data methods together. Without those elements, readers can understand the question and broad design but cannot evaluate the primary result’s size or precision.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The most consequential limitation in interpreting this trial record is that primary outcome results are not reported. There are no primary group counts, effect estimate, confidence interval, or p-value. The record therefore supports no statistical conclusion about the between-group primary comparison.

The population intended for the primary analysis is described through baseline VABS-II and functional classification criteria, but its registry wording is incomplete. The number of participants meeting those criteria, the analysis denominators, and the handling of participants without an eligible assessment are not reported in the registry record. Enrollment of 329 does not establish how many participants contributed to the primary endpoint analysis.

The intervention descriptions are brief. Details about treatment delivery, duration, target temperature, adherence, and departures from the assigned approach are not reported. The masking designation is single, but the identity of masked parties is not stated. The randomization procedure and allocation concealment are also not described.

Missing-data methods, the statistical model or test, covariate adjustment, analysis by assigned group, and sensitivity analyses are not reported in the registry record. The record lists multiple outcome measures and analyses but does not explain their relationship or describe a multiplicity plan. The safety percentages do not have a clearly stated denominator, and no inferential comparisons are reported for adverse events.

These limitations concern the information available in the registry record; they do not establish that the underlying trial lacked methods or results. They mean that the design can be described more fully than its findings can be evaluated from this record alone.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Therapeutic Hypothermia to Improve Survival After Cardiac Arrest in Pediatric Patients-THAPCA-IH [In Hospital] Trial — NCT00880087.
• Registry record last updated 2018-06-15; status last verified 2018-05.
• Results first posted 2018-06-15.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

NCT00880087 is the completed THAPCA-IH trial, a randomized, single-masked, parallel-group comparison of therapeutic hypothermia and therapeutic normothermia after in-hospital cardiac arrest in pediatric patients. The registry lists enrollment of 329, a start date of 2009-09, primary completion in 2016-02, and the University of Michigan as sponsor.

The primary endpoint combines survival at the one-year anniversary of cardiac arrest with a VABS-II score of 70 or greater assessed within the stated window. The primary analysis population was defined in part by baseline VABS-II, POPC, and PCPC criteria, but the record’s population description is incomplete. Primary outcome results and their statistical uncertainty are not reported in the registry record. Selected serious and other adverse-event counts, serious-event terms, and death counts are listed descriptively.